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Objective: We sought to examine the effects of modified venovenous ultrafiltration after cardiopulmonary bypass on pulmonary compliance in infants., Methods: We prospectively enrolled 38 infants undergoing their first operation for congenital heart disease. Infants were randomized to receive 20 minutes of modified ultrafiltration after bypass or control. Static and dynamic compliance was measured after induction of anesthesia, before and immediately after filtration in the operating theater, 1 hour after return to the pediatric intensive care unit, and 24 hours after the operation. Length of time on the ventilator, inotropic requirements, and length of stay in the intensive care unit were recorded., Results: Modified ultrafiltration produced a significant immediate improvement in dynamic (pre-ultrafiltration 2.5 +/- 1.9 mL/cm H(2)O to post-ultrafiltration 2.9 +/- 2.7 mL/cm H(2)O, P =.03) and static (pre-ultrafiltration 2.1 +/- 0.9 mL/cm H(2)O to post-ultrafiltration 2.9 +/- 2.1 mL/cm H(2)O, P =.04) compliance. However, there was no significant difference in the change in dynamic (P =.3) or static (P =.7) compliance in the ultrafiltration and control groups when compared before the operation, after the operation, and at 24 hours. There was no significant difference in the time to extubation between patients and control subjects (140 +/- 91 hours vs 90 +/- 58 hours) or the length of intensive care unit stay (10.0 +/- 9.1 days vs 7.4 +/- 5.7 days)., Conclusions: Modified ultrafiltration produces an improvement in pulmonary compliance after bypass in infants. However, these improvements are not sustained past the immediate post-ultrafiltration period and do not lead to a decreased length of intubation or intensive care unit stay.

Objectives: To examine whether coagulation tests, sampled before and during cardiopulmonary bypass (CPB), are related to blood loss and blood product transfusion requirements, and to determine what test value(s) provide the best sensitivity and specificity for prediction of excessive hemorrhage., Design: Prospective., Setting: University-affiliated, pediatric medical center., Participants: Four hundred ninety-four children., Interventions: Coagulation tests., Measurements and Main Results: Demographic, coagulation test, blood loss, and transfusion data were noted in consecutive children undergoing cardiac surgery. Laboratory tests included hematocrit (Hct), prothrombin time, partial thromboplastin time (PTT), platelet count, fibrinogen concentration, and thromboelastography. Stepwise linear regression analysis indicated that platelet count during CPB was the variable most significantly associated with intraoperative blood loss (in milliliters per kilogram) and 12-hour chest tube output (in milliliters per kilogram). Other independent variables associated with blood loss were thromboelastography maximum amplitude (MA) during CPB, preoperative PTT, preoperative Hct, and preoperative thromboelastography angle and shear modulus values. Thromboelastography MA during CPB was the only variable associated with total products transfused (in milliliters per kilogram). Of all tests studied, platelet count during CPB (< or = 108,000/microL) provided the maximum sensitivity (83%) and specificity (58%) for prediction of excessive blood loss (receiver operating characteristic analysis). Blood loss was inversely related to patient age; neonates received the most donor units (median, 8 units; range, 6 to 10 units)., Conclusions: During cardiac surgery, coagulation tests (including thromboelastography) drawn pre-CPB and during CPB are useful to identify children at risk for excessive bleeding. Platelet count during CPB was the variable most significantly associated with blood loss.

Unlabelled: In this prospective cohort study of 548 children undergoing open-heart surgery, we evaluated demographic and perioperative factors to identify variables associated with perioperative blood loss and blood product transfusions. Using multivariate analysis, younger patient age was found to be the variable most significantly associated with bleeding and transfusions. Higher preoperative hematocrit, complex surgery, lower platelet count during cardiopulmonary bypass (CPB), and longer duration of deep hypothermic circulatory arrest were also significantly associated with bleeding and transfusion. Excessive postoperative chest tube (CT) drainage was associated with intraoperative bleeding. Independently associated variables accounted for 76% of the variability in CT output measured after 2 h in intensive care. Patients were subdivided into children aged < or =1 yr (infants) and children >1 yr; infants bled more intraoperatively (P<0.005); had greater cumulative CT output at 2, 6, 12, and 24 h (P<0.0001); and received more blood products (P<0.0001). Factors associated with bleeding and transfusions varied with patient age. Lower body core temperature during CPB was highly associated with blood loss and transfusions in infants, whereas resternotomy, preoperative congestive heart failure, and prolonged duration of CPB were significant factors associated with bleeding and transfusions in children >1 yr old., Implications: Knowledge of the factors associated with blood loss and blood product transfusions can help to identify children at risk of excessive bleeding after open-heart surgery.

Objective: To compare coagulation test results, blood loss, and blood product transfusions between patients receiving prophylactic epsilon-aminocaproic acid (EACA) and a control group matched for age, resternotomy, and surgery in children undergoing cardiac surgery., Design: Nested case-control study., Setting: University-affiliated, pediatric medical center., Participants: Same study period; 70 patients in EACA group and 70 patients in control group., Interventions: Prophylactic EACA administered intravenously (load, 150 mg/kg, infusion; 30 mg/kg/h) to 70 patients at increased risk for bleeding (reoperation or Ross procedure)., Measurements and Main Results: Coagulation test values were measured before, during, and after cardiopulmonary bypass (CPB). Intraoperative blood loss, postoperative chest tube output, and allogenic blood product transfusions were recorded. Comparison of demographic and surgical data indicated close matching of the EACA and control groups. The EACA group ([median, 25th to 75th quartile] 15.6 mL/kg; 9.2 to 26.3 mL/kg) had less intraoperative blood loss than the control group (22.2 mL/kg; 14.3 to 36.3 mL/kg; p = 0.02). Postoperative chest tube output at 6 hours (p = 0.08), 12 hours (p = 0.07), and 24 hours (p = 0.08) was not significantly different between groups. Fewer EACA group patients required reexploration for bleeding (p < 0.05). There was no difference between groups in blood products transfused (in milliliters per kilogram or allogenic exposure per patient). Thromboelastography values (maximum amplitude [MA], whole blood clot lysis index at 30 minutes after MA) during CPB were better preserved in the EACA group., Conclusion: EACA reduced intraoperative blood loss but did not significantly decrease blood product transfusions. Lack of efficacy may be related to relative underdosing and should be further studied.

Objective: Thromboelastographic evaluation of the influence of fibrinolysis on blood loss and blood product transfusions in children during cardiac surgery., Design: Prospective study., Setting: University-affiliated, pediatric medical center., Participants: Two hundred seventy-eight consecutive children undergoing cardiac surgery., Interventions: Blood sampling for coagulation tests, including native and protamine-modified thromboelastography., Measurements and Main Results: Blood coagulation tests were measured before, during, and after cardiopulmonary bypass (CPB). Demographic data, perioperative blood loss, and blood product transfusions were prospectively recorded. Fibrinolysis was defined as thromboelastography of A30/MA less than 0.85 (MA, maximum amplitude; A30, amplitude 30 minutes after MA) and was noted in 3% of children pre-CPB, 16% during CPB, and 3% post-CPB. Fibrinolysis before CPB was associated with poor cardiac output. Fibrinolysis during CPB occurred in young children (aged 350 +/- 836 days) undergoing complex surgery with prolonged CPB (119 +/- 48.8 minutes) and deep hypothermia (25.6 degrees C +/- 4.7 degrees C). These patients received blood products after CPB and were not fibrinolytic after transfusion. They incurred similar blood loss (in mL/kg) and received similar volumes of blood products (mL/kg) as age-matched and surgery-matched patients without fibrinolysis., Conclusion: A group of children at risk for fibrinolysis during CPB was identified. However, fibrinolysis during CPB did not influence blood loss or the total volume of blood products transfused.

Objective: To determine if vein localization with an audio Doppler increases successful central venous cannulation and decreases complications in infants and children when performed by inexperienced operators, compared with vein localization by anatomic landmarks (ALs)., Design: A prospective cohort of infants and children undergoing central venous cannulation for cardiac surgery., Setting: A university-affiliated children's hospital with a pediatric anesthesia fellowship program., Participants: All infants and children undergoing cardiac surgery between July 1, 1996, and January 1, 1997., Interventions: Subjects had central venous catheters (CVCs) placed by an anesthesia fellow by either ALs or audio-Doppler localization of the veins., Measurements and Main Results: Eighty-four children were studied. Internal jugular vein (IJV) cannulation was attempted in 71 (85%) children and femoral vein cannulation in 13 (15%) children. Time to catheter insertion, number of needle passes, and artery puncture were noted. Sixty-one of 63 (97%) children had successful central venous cannulation by an anesthesia fellow using audio-Doppler vein localization. This was significantly greater than the 13 of 21 (62%) successful cannulations among children who had veins localized by ALs. Time to insertion did not differ by method of vein localization; however, the number of needle passes was significantly greater in the AL group. Artery puncture did not differ significantly by method of vein localization., Conclusion: Vein localization by audio Doppler significantly increases the rate of successful central venous cannulation and decreases the number of needle passes in pediatric patients when used by inexperienced operators.

Background: Peripherally inserted central venous catheters (PICCs) are commonly used intravenous access devices in children. Although PICCs are intended to be placed in central veins, many fail to reach this location. These noncentral PICCs are used for administration of medications and isotonic solutions., Objectives: To examine the efficacy of noncentral PICCs for completion of therapy, the complications associated with their use, and the effectiveness of noncentral PICCs as compared with PICCs placed in a central vein., Design: A prospective cohort study of children in whom PICCs were inserted, from January 1, 1994, to January 1, 1996., Setting: A university-affiliated teaching institution., Main Outcome Measurement: Completion of intravenous therapy., Results: A total of 587 PICCs were studied. Thirty-nine percent of PICCs were placed in noncentral veins. Centrally placed PICCs had significantly longer catheter duration compared with those placed noncentrally (16.6 vs 11.4 days, respectively). However, central and noncentral PICCs had similar therapy completion rates (73% and 69%, respectively). Catheter failure because of occlusion and accidental dislodgment were similar for central and noncentral PICCs. Likewise, complications caused by exit-site infection, phlebitis, and catheter-associated sepsis were also similar for catheters in the 2 locations. Catheter survival curves were similar for central and noncentral PICCs., Conclusions: Our study demonstrates that PICCs placed in noncentral veins provide reliable and safe intravenous access for administration of many medications and isotonic solutions for about 2 weeks' duration. The placement of PICCs in central veins may be restricted to those children who need central vascular access because of the type of intended therapy.

Injury associated with ischemia and reperfusion is a significant factor in a number of clinical diseases. We have completed a number of preclinical studies investigating the blockade of leukocyte adhesion molecules in ischemia-reperfusion injury. In our work and in the work of other investigators, monoclonal antibodies directed to CD18, P-selectin and L-selectin were effective in reducing ischemia-reperfusion injury to the rabbit ear and in reducing injury following hemorrhagic shock in both rabbits and nonhuman primates. Ischemia-reperfusion injury was also reduced by synthetic oligosaccharide sLe(x). These studies suggest that adhesion blockade might be effective in the clinical setting.

This prospective cohort study determined the incidence and risk factors for development of postdural puncture headache (PDPH) in children after lumbar puncture (LP). Eighty-six children were enrolled. LPs were performed with use of 22-gauge spinal needles with the bevel oriented parallel to the long axis of the spine. Follow-up telephone interviews and patients' diary of symptoms were collected. Headache brought on by sitting up and relieved by lying down was defined as PDPH. Of the 80 who completed the study, six (8%) developed PDPH. Two (3%) were less than 6 years old and four (5%) were 6 to 12 years of age. Children with a history of headache following a previous LP were nine times as likely to experience PDPH. PDPH occurs not infrequently in children. A prior history of headache is a predisposing factor.

Unlabelled: We investigated the pharmacokinetics and side effects of milrinone in infants and children (< or = 13 yr) after open heart surgery in this prospective, open-label study. Milrinone binding to cardiopulmonary bypass (CPB) circuitry was also examined in out two groups. Children in the small dose group (n = 11) received two 25-microg/kg boluses with a final infusion rate of 0.5 microg kg(-1) x min(-1); those in the large dose group (n = 8) received a 50-microg/kg bolus and a 25-microg/kg bolus with a final infusion rate of 0.75 microg x kg(-1) x min(-1). Blood samples for milrinone concentration were drawn 30 min after each bolus, at steady state, and after discontinuing the milrinone infusion. Pharmacokinetics were evaluated using traditional and nonlinear mixed effects modeling analysis. Milrinone kinetics best fit a two-compartment model. Steady-state plasma levels in the small and large dose groups were within the adult therapeutic range (113 +/- 39 and 206 +/- 74 ng/mL, respectively). The volumes of distribution (Vbeta) in infants (0.9 L/kg) and children (0.7 L/kg) were not different, but infants had significantly lower milrinone clearance (3.8 vs 5.9 mL x kg(-1) x min(-1)). Thrombocytopenia (defined as platelet count < or = 100,000 mm(-3)) occurred in 58%, and the risk increased significantly with duration of infusion. Tachyarrythmias were noted in two patients. Milrinone did not bind to CPB circuitry. We conclude that milrinone is cleared more rapidly in children than in adults. The major complication was thrombocytopenia., Implications: Most pediatric dosing is based on data published for adults. Infants and children have kinetics that differ from adults. We studied the distribution of I.V. milrinone in infants and children after open heart surgery. Milrinone had a larger volume of distribution and a faster clearance in infants and children than in adults, and dosing should be adjusted accordingly.

Objective: To determine the effects of red cell separation and ultrafiltration on heparin concentration., Design: Prospective study., Setting: University-affiliated, pediatric medical center., Participants: Thirty-one children undergoing cardiac surgery., Interventions: Blood sampled for heparin concentration and coagulation tests., Measurements and Main Results: Thirteen infants under-went modified veno-venous ultrafiltration (UF) after cardiopulmonary bypass (CPB). In addition, residual blood in the CPB circuit was hemoconcentrated by UF and reinfused (UF group). Heparin concentration increased from 2.0 +/- 0.6 to 2.5 +/- 0.8 U/mL, following modified UF; while activated coagulation time (ACT) decreased from 701 +/- 177 to 627 +/- 107 seconds. Heparin concentration of CPB circuit residual increased from 1.9 +/- 0.7 to 3.1 +/- 1.0 U/mL. In 18 children (older than 1 year old), the residual blood in the CPB circuit was hemoconcentrated by cell separation (CS) and reinfused (CS group). Heparin concentration of CPB circuit residual decreased from 2.6 +/- 0.6 to 0.3 +/- 0.2 U/mL. After reinfusion, patient heparin concentration remained unchanged at < 0.05 U/mL. Thrombin time increased from 28 +/- 6 to 48 +/- 29 seconds and did not correlate with H., Conclusions: The plasma concentration of heparin increased after veno-venous modified UF of the patient. Heparin concentration also increased after UF of residual CPB circuit blood. In contrast, circuit blood hemoconcentrated by CS contained minimal heparin, and, when infused, did not increase patient's heparin concentration. ACT and thrombin time did not correlate with heparin concentration.

Leukocyte emigration in the lung occurs by both CD18-dependent and -independent mechanisms that are stimulus specific. We examined the effect of CD18 blockade (mAb 60.3) on neutrophil (PMN) emigration into, and bacterial clearance from, the lung. After intravenous treatment with either mAb 60.3 or saline, rabbits were given an intralobar inoculation with 10(9) colony-forming units of either Staphylococcus aureus or Escherichia coli. Four hours after inoculation, lungs were lavaged to assess PMN emigration. CD18 blockade reduced PMN emigration to E. coli by 76% but only 45% to S. aureus. Experiments to determine bacterial recovery from the lungs at 4, 8, and 24 h after inoculation showed that CD18 blockade impaired the early (4 h) clearance of E. coli but not S. aureus. These findings suggest that PMN emigration to intrapulmonary S. aureus is largely CD18-independent. In contrast, intrapulmonary E. coli elicits CD18-mediated PMN emigration. CD18 blockade results in impaired clearance of E. coli but not S. aureus from the lung.

Background: Human newborns, particularly those born before full term, are more susceptible to bacterial infections as a result of impaired host defense mechanisms. Compared with adults, circulating leukocytes from human newborns (preterm and full-term gestations) and newborn rabbits (full-term gestation) have low resting levels of CD62L (L-selectin) and do not significantly increase surface expression of CD18 after inflammatory stimulation. To determine the potential utility of preterm rabbits in investigations of perinatal human conditions, the authors compared the surface expression of the beta 2-integrin CD18 and CD62L (L-selectin) on polymorphonuclear leukocytes (PMNs) from perinatal rabbits and perinatal humans, both under resting conditions and after in vitro activation with inflammatory stimulants., Methods: After erythrocyte lysis of whole-blood samples, leukocytes from 7-day-old, full-term (31-day gestation), and preterm (24-day gestation) rabbits, as well as full-term (37-42 week gestation) and preterm (27-36 week gestation) human newborns were prepared and stimulated in vitro at 37 degrees C with either C5a or phorbol myristate acetate. After fluorescence labeling of CD18 and CD62L with monoclonal antibodies, PMN adhesion molecule expression was assessed by flow cytometry., Results: Constitutive CD18 expression was not significantly different between perinatal and adult humans but was reduced in all perinatal rabbits compared with adults. Inflammatory stimulation caused significant increases in CD18 expression in adult human PMNs but not in full-term and preterm newborns. Changes in CD18 expression in adult and preterm rabbits after stimulation, although in the same direction as humans, were more variable. In both species, constitutive CD62L expression on PMNs from all perinates was significantly lower than in adults. However, CD62L was shed to similar degrees after inflammatory stimulation in all groups., Conclusions: Preterm rabbits may provide a potentially useful experimental model to study PMN adhesion and host defense in the perinatal period, particularly preterm gestations. Specific advantages and limitations of rabbits in such studies are discussed.

Objective: Use of peripherally inserted central venous catheters (PICCs) to provide prolonged intravenous (IV) access in children is increasing. Our goal was to describe the children treated with PICCs in our institution, and to study catheter features such as catheter life, completion of therapy, and complications. Furthermore, we also evaluated PICC use in children completing therapy after discharge from our institution., Methods: A prospective study of all PICCs inserted at the Children's Hospital and Medical Center (CHMC), a university-affiliated teaching institution, during a period of 18 months (January 1994 to July 1995)., Results: A total of 441 PICCs were inserted in 390 patients. Patient age ranged from 0 to 22 years with a mean of 5.4 +/- 6.0 years. No insertion complications occurred. Treatment of infectious disease (46%) was the most frequent reason for PICC insertion. All pediatric medical and surgical services used PICCs. Average catheter life was 13 +/- 12 days. Sixty-one percent of PICCs were used entirely at CHMC, while 39% were also used at home or at an outside hospital. Completion of therapy was achieved in 69% of PICCs. Among children who completed therapy outside our hospital, there was no difference in the rates of occlusion, accidental dislodgment, or infection. One hundred twenty-nine (29%) PICCs were removed for complications. Occlusion (7%), accidental displacement (8%), and suspicion of sepsis (8%) were the most common complications. Only 2% of PICCs had documented catheter-associated sepsis., Conclusions: PICCs provide reliable and safe access for prolonged IV therapy in neonates and children. The low incidence of complications with PICCs make them an attractive device for prolonged IV access. Similar complication rates with use in and out of hospital suggest that home IV therapy can be safely delivered with PICCs, avoiding expensive hospitalization.

Leukocyte adhesion molecule (LAM) blockade reduces ischemia-reperfusion injury. We tested the hypothesis that a monoclonal antibody (MAb) that recognizes a functional epitope of L-selectin would decrease hemorrhagic shock-induced reperfusion injury. Anesthetized rabbits were subjected to 2 h of hemorrhagic shock (cardiac output reduced to 30% of baseline), then given one of the following treatments: MAbs that recognize functional domains of L-selectin (LAM1-3), CD18 (60.3), MAbs that recognize a nonfunctional domain on L-selectin (LAM1-14), or saline, immediately before resuscitation with shed blood. Additional fluids were administered as needed to maintain cardiac output at baseline levels for 6 h. The cumulative fluid resuscitation after MAb LAM1-3 (58 +/- 34 ml/kg) was not significantly different from after MAb 60.3 (21 +/- 24 ml/kg) or MAb LAM1-14 (66 +/- 51 ml/kg), but it was significantly less than saline-treated controls (142 +/- 142 ml/kg). However, two animals treated with MAb LAM1-14 died before 6 h. If their resuscitation volumes are projected to 6 h by linear regression, then the LAM1-14-treated group required significantly greater volume (101 +/- 99 ml/kg) than the MAb LAM1-3-treated group. We conclude that MAbs to a functional domain on L-selectin are protective against reperfusion-injury following hemorrhagic shock.

After Fontan repair in children, we performed a prospective, open-label study to evaluate the effect of amrinone on pulmonary vascular resistance (PVRI). Eight patients who underwent the Fontan repair had baseline arterial pressure, left atrial pressure, central venous pressure, and cardiac output measured postoperatively. Hemodynamic measurements were repeated after amrinone 4.5 mg/kg. The PVRI tended to decrease, but the change was not statistically significant. Although the systemic vascular resistance decreased to 802 +/- 222 from 941 +/- 191 dynes.s.cm-5.m-2 (P < 0.05), mean arterial blood pressure was unchanged. Cardiac index (3.8 +/- 1.2 to 4.7 +/- 1.6 L.min-1.m-2) and stroke volume index (23.6 +/- 6.7 to 30.5 +/- 8.1 mL.beat-1.m-2) increased, and heart rate decreased (160 +/- 21 to 151 +/- 24 bpm) (P < 0.05). Colloid transfusion during amrinone bolus administration was 13.9 mL/kg. The mean serum amrinone concentration was 4.2 micrograms/mL at the end of bolus and clearance was 2.24 mL.kg-1.min-1. Arrhythmias and thrombocytopenia were not noted. We conclude that amrinone administration is effective in increasing cardiac output in children who have undergone a Fontan repair.

Background and Methods: The correlations between continuous positive-pressure ventilation-induced antidiuresis/antinatriuresis, atrial transmural pressure, and atrial natriuretic peptide concentrations have not been clarified. The purpose of the present study was to use aggressive hydration to restore atrial transmural pressure during continuous positive-pressure ventilation and to test for correlations of atrial transmural pressure, atrial natriuretic peptide concentration, diuresis, and natriuresis during this intervention. An intrapleural catheter was used to measure atrial transmural pressure in three ways: a) right atrial pressure minus intrapleural pressure, b) left ventricular end-diastolic pressure minus intrapleural pressure, and c) pulmonary artery occlusion pressure minus intrapleural pressure. Hemodynamic, atrial natriuretic peptide concentrations, and renal measurements were made in 12 anesthetized closed-chest dogs during baseline (intermittent positive-pressure ventilation), during continuous positive-pressure ventilation), during continuous positive-pressure ventilation with 10 cm H2O end-expiratory pressure, and during continuous positive-pressure ventilation plus aggressive hydration (approximately 60 mL/kg lactated Ringer's solution). Pearson's correlation matrix was used to generate all possible correlation coefficients between the three atrial transmural pressures, atrial natriuretic peptide concentrations, urine output, and urine sodium excretion., Results: Application of continuous positive-pressure ventilation resulted in a 60% decrease in right atrial transmural pressure (p less than .05), a 51% decrease in left ventricular end-diastolic transmural pressure (p less than .05), and a 26% decrease in pulmonary artery occlusion transmural pressure (p less than .05) from baseline. Plasma atrial natriuretic peptide concentration decreased from 80 +/- 12 (SEM) pg/mL at baseline to 49 +/- 8 pg/mL during continuous positive-pressure ventilation (p less than .05). Both urine output and sodium excretion decreased by 81% (p less than .05). After aggressive hydration with lactated Ringer's solution during continuous positive-pressure ventilation, to restore atrial transmural pressure to baseline, plasma atrial natriuretic peptide concentration returned to baseline values (81 +/- 12 pg/mL) as did urine output and sodium excretion. Correlation indices (r2 values) between transmural pressure, atrial natriuretic peptide concentration, urine output, and sodium excretion ranged from .835 to .994. Multivariate analysis of covariance demonstrated significant (p less than .05) temporal dependence between the three transmural pressures, atrial natriuretic peptide concentration, urine output, and sodium excretion., Conclusions: The results demonstrate that aggressive hydration during continuous positive-pressure ventilation will restore diuresis and natriuresis and that this response correlates significantly with atrial transmural filling pressure and plasma atrial natriuretic peptide concentration.